Lactoferrin in Food Systems: Functional Properties, Manufacturing Technologies, and Regulatory Aspects

Relevance. Lactoferrin is a natural cationic iron-binding glycoprotein naturally present in animals and humans, particularly in human and bovine colostrum and milk. Its multifunctional properties, including antimicrobial, immunomodulatory, and antioxidant activity, have generated significant interest in its use as a food ingredient, dietary supplement, and component of functional foods.

Methods. A keyword search for potentially relevant articles was conducted in electronic databases and open-access internet searches.

Results. The use of lactoferrin is a potentially promising area for the food industry due to its enhanced immunomodulatory and antioxidant effects, as well as its extended shelf life. Today, lactoferrin is most actively used as a dietary supplement for infant formulas, specialized milk- and whey-based dairy products, processed meat products, and dietary supplements. The global lactoferrin market faces certain challenges: the development of new, more efficient methods for purifying and producing lactoferrin, as well as the open question of the legal nature of the use of lactoferrin (including recombinant).

1. Mamontova T.V., Srinivas P.P. Lactoferrin — the future of the food industry. Proceedings of the IV Annual International Scientific and Practical Readings of the Stavropol Institute of Cooperation (branch) of the Belgorod University of Cooperation, Economics and Law: Collection of IV International Conferences of Faculty and Postgraduate Students of the Stavropol Institute of Cooperation (branch) of the Belgorod University of Cooperation, Economics and Law. Stavropol: Limited Liability Company «Publishing and Information Center «Fabula». 2018; 194–196. EDN VKIHSC

2. Ashraf M.F. et al. Nutraceutical and Health-Promoting Potential of Lactoferrin, an Iron-Binding Protein in Human and Animal: Current Knowledge. Biological trace element research. 2024; 202(1): 56–72. https://doi.org/10.1007/s12011-023-03658-4

3. Demir R., Sarıtaş S., Bechelany M., Karav S. Lactoferrin: Properties and Potential Uses in the Food Industry. International Journal of Molecular Sciences. 2025; 26(4): 1404. https://doi.org/10.3390/ijms26041404

4. Konadaka S.R. et al. Biopharming of Lactoferrin: Current Strategies and Future Prospects. Pharmaceutics. 2025; 17(8): 1023. https://doi.org/10.3390/pharmaceutics17081023

5. Zhilyakova E.T. et al. Properties and Prospects of Application of the Whey Protein Lactoferrin in Medicine and Veterinary Medicine (Review). Drug development & registration. 2022; 11(1): 32–39 (in Russian). https://doi.org/10.33380/2305-2066-2022-11-1-32-39

6. Sadovskaya, T.N. Lactoferrin, its properties, production, and application in animal husbandry and veterinary medicine. Fundamental and applied science: topical issues of theory and practice: A collection of articles from the IV International Scientific and Practical Conference. Penza: Science and Education (Gulyaev G.Yu.), 2023; 66–70 (in Russian). EDN SQQLXX

7. Trubitsina T.P. et al. Problems and Prospects of Using Recombinant Human Lactoferrin and Its Derivatives. Problems of Biology of Productive Animals. 2018; 4: 5–26. (in Russian). https://doi.org/10.25687/1996-6733.prodanimbiol.2018.3.5-26

8. Agostoni C.V. et al. EFSA Publication. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on bovine lactoferrin: EFSA-Q-2010-01269. Parma, Italy: European Food Safety Authority, 2012. https://doi.org/10.2903/j.efsa.2012.2701

9. Hu C., Shen W., Xia Y., Yang H., Chen X. Lactoferrin: Current situation and future prospects. Food Bioscience. 2024; (62): 105183. https://doi.org/10.1016/j.fbio.2024.105183

10. Wang B., Timilsena Y.P., Blanch E., Adhikari B. Lactoferrin: Structure, function, denaturation and digestion. Critical Reviews in Food Science and Nutrition. 2019; 59(4): 580–596.

11. Baker E.N., Baker H.M. A structural framework for understanding the multifunctional character of lactoferrin. Biochimie. 2009; 91(1): 3–10. https://doi.org/10.1016/j.biochi.2008.05.006.

12. González-Chávez S.A., Arévalo-Gallegos S., Rascón-Cruz Q. Lactoferrin: Structure, Function and Applications. International Journal of Antimicrobial Agents. 2008; 33: 301.e1–301.e8. https://doi.org/10.1016/j.ijantimicag.2008.07.020

13. Zorina V.N. Structure and Inhibitory Activity of Lactoferrin Against the Influenza Virus. Infection and Immunity. 2020; 1: 49–54 (in Russian). https://doi.org/10.15789/2220-7619-POL-1156

14. Lönnerdal B. Nutritional and physiologic significance of human milk proteins. The American Journal of Clinical Nutrition. 2003; 77(6): 1537S–1543S. https://doi.org/10.1093/ajcn/77.6.1537S

15. Siqueiros-Cendón T., Arévalo-Gallegos S., Iglesias-Figueroa B.F., García-Montoya I.A., Salazar-Martínez J., Rascón-Cruz Q. Immunomodulatory effects of lactoferrin. Acta Pharmacologica Sinica. 2014; 35(5): 557–566. https://doi.org/10.1038/aps.2013.200

16. Goldman I.L., Deikin A.V., Sadchikova E.R. Human Lactoferrin Can Be Alternative to Antibiotics. Proceedings of the World medical conference. Malta: WSEAS Press, 2010; 27–38. https://www.elibrary.ru/fiaxce

17. Jahani S, Shakiba A, Jahani L The Antimicrobial effect of lactoferrin on Gram-negative and Gram-positive bacteria. International Journal of Infection. 2015; 2(3): e27954. https://doi.org/10.17795/iji27594

18. Ongena R., Dierick M., Vanrompay D., Cox E., Devriendt B. Lactoferrin impairs pathogen virulence through its proteolytic activity. Frontiers in Veterinary Science. 2024; 11: 1428156. https://doi.org/10.3389/fvets.2024.1428156

19. Kutila T., Pyörälä S., Saloniemi H., Kaartinen L. Antibacterial effect of bovine lactoferrin against udder pathogens. Acta Veterinaria Scandinavica. 2003; 44(1): 1–8. https://doi.org/10.1186/1751-0147-44-35

20. Titov E.I., Tikhomirova N.A., Ionova I.I. Isolation and study of the iron-binding capacity of cow’s milk lactoferrin. Nutrition Issues. 2019; 88(1): 91–96 (in Russian). https://doi.org/10.24411/0042-8833-2019-10011

21. Kim J.W., Lee J.S., Choi Y.J., Kim C. The Multifaceted Functions of Lactoferrin in Antimicrobial Defense and Inflammation. Biomolecules. 2025; 15(8): 1174. https://doi.org/10.3390/biom15081174

22. Garda-Montoya I.A. et al. Lactoferrin a multiple bioactive protein. Biochimica et Biophysica Acta. 2011; 1820(3): 226–236. https://doi.org/10.1016/j.bbagen.2011.06.018

23. Dierick M, Van der Weken H., Rybarczyk J., Vanrompay D., Devriendt B., Cox E. Porcine and bovine forms of lactoferrin inhibit growth of porcine enterotoxigenic Escherichia coli and degrade its virulence factors. Applied and Environmental Microbiology. 2020; 86: 1–15. https://doi.org/10.1128/AEM.00524-20

24. Luna-Castro S., Aguilar-Romero F., Samaniego-Barrón L., Godínez-Vargas D., De La Garza M. Effect of bovine apo-lactoferrin on the growth and virulence of Actinobacillus pleuropneumoniae. Bio Metals. 2014; 27: 891–903. https://doi.org/10.1007/s10534-014-9752-5

25. Xu G. et al. Lactoferrin-derived peptides and lactoferricin chimera inhibit virulence factor production and biofilm formation in Pseudomonas aeruginosa. Journal of Applied Microbiology. 2010; 109: 1311–1318. https://doi.org/10.1111/j.1365-2672.2010.04751.x

26. Berlutti F. et al. Both lactoferrin and iron influence aggregation and biofilm formation in Streptococcus mutans. Biometals. 2004; 17: 271–278. https://doi.org/10.1023/B:BIOM.0000027704.53859.d3

27. Samokhina L.S. et al. Bifidogenic properties of lactoferrin peptides from cow’s milk. Issues of Biological, Medical, and Pharmaceutical Chemistry. 2016; 2: 49–53 (in Russian). EDN VRXWBP

28. Pang C.N., Lai Y.W., Campbell L.T., Chen S.C., Carter D.A., Wilkins M.R. Transcriptome and network analyses in Saccharomyces cerevisiae reveal that amphotericin B and lactoferrin synergy disrupt metal homeostasis and stress response. Scientific reports. 2017; 7: 40232. https://doi.org/10.1038/srep40232

29. Fernandes K.E., Weeks K., Carter D.A. Lactoferrin is broadly active against yeasts and highly synergistic with amphotericin B. Antimicrobial agents and chemotherapy. 2020; 64(5): e02284–19. https://doi.org/10.1128/aac.02284-19

30. Brouwer C. et al. Synthetic Human Lactoferrin Peptide hLF(1-11) Shows Antifungal Activity and Synergism with Fluconazole and Anidulafungin Towards Candida albicans and Various Non-Albicans Candida Species, Including Candidozyma auris. Antibiotics (Basel, Switzerland). 2025; 14(7): 671. https://doi.org/10.3390/antibiotics14070671

31. Fernandes K.E., Carter D.A. The antifungal activity of lactoferrin and its derived peptides: mechanisms of action and synergy with drugs against fungal pathogens. Frontiers in microbiology. 2017; 8: 2. https://doi.org/10.3389/fmicb.2017.00002

32. Legrand D., Pierce A., Elass E., Carpentier M., Mariller C., Mazurier J. Lactoferrin structure and functions. Bioactive Components of Milk. 2008; 606: 163–194. https://doi.org/10.1007/978-0-387-74087-4_6

33. García-Montoya I.A., Cendón T.S., Arévalo-Gallegos S., Rascón-Cruz Q. Lactoferrin a multiple bioactive protein: an overview. Biochimica et Biophysica Acta. 2012; 1820(3): 226–236. https://doi.org/10.1016/j.bbagen.2011.06.018

34. Duarte D.C., Nicolau A., Teixeira J.A., Rodrigues L.R. The effect of bovine milk lactoferrin on human breast cancer cell lines. Journal of Dairy Science. 2011; 94: 66–76. https://doi.org/10.3168/jds.2010-3629

35. Marchetti M., Superti F., Ammendolia M.G., Rossi P., Valenti P., Seganti L. Inhibition of poliovirus type 1 infection by iron-, manganese-, and zinc-saturated lactoferrin. Medical Microbiology and Immunology (Berlin). 1999; 187: 199–204. https://doi.org/10.1007/s004300050093

36. Rodríguez D.A., Vázquez L., Ramos G. Actividad Antimicrobiana de la lactoferrina: Mecanismos and aplicaciones clínicas potenciales. Revista Latinoamericana de Microbiología. 2005; 47: 102–111 (in Spanish).

37. Zhuravlev D.E., Salmanova D.A. Analysis of the biological activity of lactoferrin obtained from various types of dairy raw materials. Food Innovations and Biotechnology: Collection of Abstracts of the XIII All Russian (National) Scientific Conference of Students, Postgraduates, and Young Scientists. Kemerovo: Kemerovo State University, 2025; 255–257 (in Russian). EDN RMBIIR

38. Jańczuk A., Brodziak A., Czernecki T., Król J. Lactoferrin — The health-promoting properties and contemporary application with genetic aspects. Foods. 2022; 12(1): 70.

39. Sienkiewicz M., Jaśkiewicz A., Tarasiuk A., Fichna J. Lactoferrin: An overview of its main functions, immunomodulatory and antimicrobial role, and clinical significance. Critical reviews in food science and nutrition. 2022; 62(22): 6016–6033.

40. Hassan M.A., Abedelmaksoud T.G., Abd El-Maksoud A.A. Effects of Lactoferrin Supplemented with Fermented Milk on Obesity Associated Pancreatic Damage in Rats. Life. 2022; 12(12): 2019. https://doi.org/10.3390/life12122019

41. Del Olmo A., Calzada J., Nuñez Manuel M. Effect of lactoferrin and its derivatives against gram-positive bacteria in vitro and, combined with high pressure, in chicken breast fillets. Meat Science. 2012; 90(1): 71–76. https://doi.org/10.1016/j.meatsci.2011.06.003

42. Franco I., Pérez M.D., Conesa C., Calvo M., Sánchez L. Effect of technological treatments on bovine lactoferrin: An overview. Food Research International. 2018; 106: 173–182. https://doi.org/10.1016/j.foodres.2017.12.016

43. Mizuki M. et al. Effect of lactoferrin on prevention of infectious diseases in winter: a randomized, double-blinded, placebo-controlled trial. In: Abstract Book of the 14th International Conference on Lactoferrin Structure, Function and Applications. Peru, 2019; 66.

44. Paesano R., Berlutti F., Pietropaoli M., Goolsbee W., Pacifici E., Valenti P. Lactoferrin efficacy versus ferrous sulfate in curing iron disorders in pregnant and non-pregnant women. International Journal of Immunopathology and Pharmacology. 2010; 23: 577–587. https://doi.org/10.1177/039463201002300220

45. Saeed M., Hussain N., Ahmed S., Khan R.U., Andoh V., Husain S., Huayou C. The Potential of Lactoferrin: A Call for Future Research in Poultry Nutrition. World’s Poultry Science Journal. 2023; 79: 731–750.

46. Kiani A.K., Bonetti G., Donato K., Bertelli M. Dietary supplements for intestinal inflammation. Journal of Preventive Medicine and Hygiene. 2022; 63(2 Suppl 3): E214–E220. https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2763

47. Rondanelli M, Gasparri C, Cavioni A, Sivieri C, Barrile GC, Mansueto F, Perna S. A Patented dietary supplement (hydroxy methyl-butyrate, carnosine, magnesium, butyrate, lactoferrin) is a promising therapeutic target for age-related sarcopenia through the regulation of gut permeability: A randomized controlled trial. Nutrients. 2024; 16(9): 1369. https://doi.org/10.3390/nu16091369

48. Amouheydari M., Ehsani M.R., Javadi I. Effect of a dietary supplement composed of hydrolyzed milk proteins and vanillin on the reduction of infection and oxidative stress induced by chemotherapy. Journal of Food Biochemistry. 2020; 44(10): e13434. https://doi.org/10.1111/jfbc.13434

49. Harouna S. et al. Effect of hydrolysis and microwave treatment on the antibacterial activity of native bovine milk lactoferrin against cronobacter sakazakii. International Journal of Food Microbiology. 2020; 319: Article 108495. https://doi.org/10.1016/j.ijfoodmicro.2019.108495

50. Adnan A. et al. Effect of lactoferrin supplementation on composition, fatty acids composition, lipolysis and sensory characteristics of cheddar cheese. International Journal of Food Properties. 2023; 26(1): 437–452. https://doi.org/10.1080/10942912.2023.2166953

51. Serrano G. et al. Liposomal Lactoferrin as Potential Preventative and Cure for COVID-19. International Journal of Research in Health Sciences. 2020; 8(1): 8–15. https://doi.org/10.5530/ijrhs.8.1.3

52. Wolf J.S. et al. Oral lactoferrin results in T cell-dependent tumor inhibition of head andneck squamous cell carcinoma in vivo. Clinical Cancer Research. 2007; 13(5): 1601–1610. https://doi.org/10.1158/1078-0432.CCR-06-2008

53. Onishi J., Roy M.K., Juneja L.R., Watanabe Y., Tamai Y. A lactoferrin-derived peptide with cationicresidues concentrated in a region of its helical structure induces necrotic cell death in a leukemic cell line. Journal of Peptide Science. 2008; 14: 1032–1038. https://doi.org/10.1002/psc.1039

54. Kanwar J.R. et al. ‘Iron-saturated’ lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy. Immunology & Cell Biology. 2008; 86: 277–288.

55. Arcella A. et al. In vitro and in vivo effect of human lactoferrin on glioblastoma growth. Journal of Neurosurgery. 2015; (123): 1026 1035

56. Hong R. et al. A Review of the Biological Activities of Lactoferrin: Mechanisms and Potential Applications. Food & Function. 2024; 15: 8182–8199.

57. Sarıtaş S. et al. The Impact of Fermentation on the Antioxidant Activity of Food Products. Molecules. 2024; 29: 3941.

58. Kaplan M. et al. Production of Bovine Colostrum for Human Consumption to Improve Health. Frontiers in Pharmacology. 2022; 12: 796824.

59. Jańczuk A., Brodziak A., Król J., Czernecki T. Properties of Yoghurt Fortified in Lactoferrin with Effect of Storage Time. Animals. 2023; 13(10): 1610. https://doi.org/10.3390/ani13101610

60. Tsukahara T., Fujimori A., Misawa Y., Oda H., Yamauchi K., Abe F., Nomiyama T. The Preventive Effect of Lactoferrin-Containing Yogurt on Gastroenteritis in Nursery School Children — Intervention Study for 15 Weeks. International Journal of Environmental Research and Public Health. 2020; 17(7): 2534. https://doi.org/10.3390/ijerph17072534

61. Palmano K.P., Ramos R., Watson M., Callon K.E., Cornish J. Survival and Bone-Active Properties of Bovine Lactoferrin Supplemented into Stirred Yoghurt. International Dairy Journal. 2011; 21: 477–483.

62. Fetouh M., Elbarbary H., Ibrahim E., Maarouf A. Afifi Effect of Adding Lactoferrin on Some Foodborne Pathogens in Yogurt. Iranian Journal of Veterinary Medicine. 2023; 17(3): 189–198. https://doi.org/10.32598/ijvm.17.3.1005313

63. Nadi W.G., Taher E.M., Awad A.A.N., Ahmed L.I. Lactoferrin’s potential application in enhancing yoghurt’s microbial and sensory qualities, with emphasis on the starter culture activity. Journal of Dairy Research. 2023; 90(4): 403–408. https://doi.org/10.1017/S0022029923000675

64. Shishir M.R.I., Suo H., Taip F.S., Cheng K.W. Lactoferrin-chia seed mucilage complex coacervates for intestinal delivery of quercetin and fortification of set yogurt. Food Chemistry. 2024; 456: 139818. https://doi.org/10.1016/j.foodchem.2024.139818

65. Franco I., Castillo E., Pérez M.D., Calvo M., Sánchez L. Effect of bovine lactoferrin addition to milk in yogurt manufacturing. Journal of Dairy Science. 2010; 93(10): 4480–4489. https://doi.org/10.3168/jds.2009-3006

66. Naidu A.S. Activated lactoferrin - A new approach to meat safety. Food Technology. 2002; 56(3): 40–45.

67. Bobreneva I.V., Rokhlova M.V. Lactoferrin: properties and application. A review. Theory and practice of meat processing. 2021; 6(2): 128–134. https://doi.org/10.21323/2414-438X-2021-6-2-128-134

68. Bravo D., de Alba M., Medina M. Combined treatments of high pressure with the lactoperoxidase system or lactoferrin on the inactivation of listeria monocytogenes, salmonella enteritidis and escherichia coli O157: H7in beef carpaccio. Food Microbiology. 2014; 41: 27–32. https://doi.org/10.1016/j.fm.2014.01.010

69. De Alba M., Bravo D., Medina M. Inactivation of listeria monocytogenes and salmonella enteritidis in dry-cured ham by combined treatments of high pressure and the lactoperoxidase system or lactoferrin. Innovative Food Science and Emerging Technologies. 2015; 31: 54–59. https://doi.org/10.1016/j.ifset.2015.06.013

70. Montiel R., Martín-Cabrejas I., Medina M. Reuterin, lactoperoxidase, lactoferrin and high hydrostatic pressure on the inactivation of food-borne pathogens in cooked ham. Food Control. 2015; 51: 122–128. https://doi.org/10.1016/j.foodcont.2014.11.010

71. Montiel R., Martín-Cabrejas I., Peirotén Á., Medina M. Reuterin, lactoperoxidase, lactoferrin and high hydrostatic pressure treatments on the characteristics of cooked ham. Innovative Food Science and Emerging Technologies. 2016; 35: 111–118. https://doi.org/10.1016/j.ifset.2016.04.013

72. Adnan A. et al. Effect of Lactoferrin Supplementation on Composition, Fatty Acids Composition, Lipolysis and Sensory Characteristics of Cheddar Cheese. International Journal of Food Properties. 2023; 26: 437–452.

73. Ali E., Atteya L., Farag E., Helmy N., Nabil M. The Effect of Using Edible Coating Fortified with Lactoferrin on the Shelf Life of Oriental Sausage. Benha Veterinary Medical Journal. 2023; 45: 215–220.

74. Elsayed H., Hussei D.E.D.E. Hussein Impact of Different Concentrations of Lactoferrin on the Shelf Life of the Chilled Chicken Breast. Taiwanese Journal of Agricultural Chemistry and Food Science. 2022; 60.

75. Li F. et al. Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial. The Journal of Pediatrics. 2019; 215: 24-31. e8. https://doi.org/10.1016/j.jpeds.2019.08.030

76. Chen K. et al. Dose Effect of Bovine Lactoferrin Fortification on Iron Metabolism of Anemic Infants. Journal of Nutritional Science and Vitaminology (Tokyo). 2020; 66(1): 24–31. https://doi.org/10.3177/jnsv.66.24

77. Tarnow-Mordi W.O. et al. The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial. The Lancet Child & Adolescent Health. 2020; 4(6): 444–454. https://doi.org/10.1016/S2352-4642(20)30093-6

78. Sawale M., Ozadali F., Valentine C.J., Benyathiar P., Drolia R., Mishra D.K. Impact of Bovine Lactoferrin Fortification on Pathogenic Organisms to Attenuate the Risk of Infection for Infants. Food Control. 2022; 139: 109078.

79. Motoki N. et al. Effects of Lactoferrin-Fortified Formula on Acute Gastrointestinal Symptoms in Children Aged 12–32 Months: A Randomized, Double-Blind, Placebo-Controlled Trial. Frontiers in Pediatrics. 2020; 8: 233.

80. Chen K. et al. Effect of bovine lactoferrin from iron-fortified formulas on diarrhea and respiratory tract infections of weaned infants in a randomized controlled trial. Nutrition (Burbank, Los Angeles County, Calif.). 2016; 32: 222–227. https://doi.org/10.1016/j.nut.2015.08.010

81. Ishikado A. et al. Liposomal lactoferrin induced significant increase of the interferon-alpha (IFN-alpha) producibility in healthy volunteers. BioFactors (Oxford, England). 2004; 21: 69–72. https://doi.org/10.1002/biof.552210113

82. Acero-Lopez A., Schell P., Corredig M., Alexander M. Characteri zation of Lactoferrin oil-in-water Emulsions and Their Stability in Recombined Milk. Journal of Dairy Research. 2010; 77(4): 445–451. https://doi.org/10.1017/S0022029910000622

83. Abad I., Conesa C., Sánchez L. Development of Encapsulation Strategies and Composite Edible Films to Maintain Lactoferrin Bioactivity: A Review. Materials (Basel). 2021; 14(23): 7358. https://doi.org/10.3390/ma14237358

84. Tavassoli M. et al. Methylcellulose/Chitosan Nanofiber-Based Composites Doped with Lactoferrin-Loaded Ag-MOF Nanoparticles for the Preservation of Fresh Apple. International Journal of Biological Macromolecules. 2024; 259: 129182.

85. Tu M. et al. Identification of Dual-Function Bovine Lactoferrin Peptides Released Using Simulated Gastrointestinal Digestion. Food Bioscience. 2021; 39: 100806.

86. Kowalczyk P., Kaczyńska K., Kleczkowska P., Bukowska-Ośko I., Kramkowski K., Sulejczak D. The Lactoferrin Phenomenon — A Miracle Molecule. Molecules 2022; 27: 2941.

87. Bolat E. et al. Polyphenols: Secondary Metabolites with a Biological Impression. Nutrients 2024; 16: 2550.

88. Kaczmarek K.A., Kosewski G., Dobrzyńska M., Drzymała-Czyż S. Lactoferrin Production: A Systematic Review of the Latest Analytical Methods. Applied Sciences. 2025; 15(8):4540. https://doi.org/10.3390/app15084540

89. Sharma A., Gupta G., Ahmad T., Kaur B., Hakeem K.R. Tailoring Cellular Metabolism in Lactic Acid Bacteria through Metabolic Engineering. Journal of Microbiological Methods. 2020; 170: 105862. https://doi.org/10.1016/j.mimet.2020.105862

90. Van Der Strate B.W.A., Belijaars L., Molema G., Harmsen M.C., Meijer D.K.F. Antiviral activities of lactoferrin. Antiviral Research. 2001; 52: 225–239. https://doi.org/10.1016/s0166-3542(01)00195-4

91. Tomita M., Wakabayashi H., Yamauchi K., Teraguchi S., Hayasawa H. Bovine lactoferrin and lactoferricina derived from milk: production and applications. Biochemistry and Cell Biology. 2002; 80: 109–112. https://doi.org/10.1139/o01-230

92. Stowell K.M., Rado T.A., Funk W.D., Tweedie J.W. Expression of cloned human lactoferrin in baby-hamster kidney cells. Biochemical Journal. 1991; 276: 349–355. https://doi.org/10.1042/bj2760349

93. Ward P.P., Piddington C.S., Cunningham G., Zhou X., Wyat R., Conneely O. A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic. Nature Biotechnology. 1995; 13: 498–503. https://doi.org/10.1038/nbt0595-498

94. Chen H.L. et al. Probiotic Lactobacillus casei expressing human lactoferrin elevates antibacterial activity in the gastrointestinal tract. BioMetals. 2010; 23: 543–554. https://doi.org/10.1007/s10534-010-9298-0.

95. Zhang D.B., Jiang Y.L., Wu X.F., Hong M.M. Expression of human lactoferrin cDNA in insect cells. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica. 1998; 30: 575–578.

96. Liu T., Zhang Y.Z., Wu X.F. High level expression of functionally active human lactoferrin in silkworm larvae. Journal of Biotechnology. 2005; 118: 245–256. https://doi.org/10.1016/j.jbiotec.2005.05.005

97. Zhang Z., Coyne D., Vidaver A., Mitra A. Expression of human lactoferrin cDNA confers resistance to Ralstonia sdanacearum in transgenic tobacco plants. Phytopathology. 1998; 88: 730–734. https://doi.org/10.1094/PHYTO.1998.88.7.730

98. Nguyen T.C., Lakshaan D.K., Han J., Galvez L., Mitra A. Transgenic plants expressing antimicrobial lactoferrin protein are resistant to a fungal pathogen. Journal of plant molecular biology & biotechnology. 2011; 2: 1–8.

99. Nandi S., Yalda D., Lu S., Nikolv Z., Misaki R., Fujiyama K., Huang N. Process development and economic evaluation of recombinant human lactoferrin expressed in rice grain. Transgenic Research. 2005; 14: 237–249. https://doi.org/10.1007/s11248-004-8120-6

100. Suzuki Y., Kelleher S., Yalda D., Wu L., Huang J., Huang N., Lӧnnerdal B. Expression, characterization, and biologic activity of recombinant human lactoferrin in rice. Journal of Pediatric Gastroenterology and Nutrition. 2003; 36: 190–199. https://doi.org/10.1097/00005176-200302000-00007

101. Conesa C., Calvo M., Sánchez L. Recombinant human lactoferrin: a valuable protein for pharmaceutical products and functional foods. Biotechnology Advances. 2010; 28: 831–838. https://doi.org/10.1016/j.biotechadv.2010.07.002

102. Tian Z.G. et al. Multimerization and fusion expression of bovine lactoferrin derivative Lfcin B15-W4, 10 in Escherichia coli. Applied Microbiology and Biotechnology. 2007; 75: 117–124. https://doi.org/10.1007/s00253-006-0806-7

103. Feng X.J. et al. Fusion expression of bovine lactoferricin in Escherichia coli. Protein Expression and Purification. 2006; 47: 110–117. https://doi.org/10.1016/j.pep.2005.08.016

104. Chen G.H., Yin L.J., Chiang I.H., Jiang S.T. Expression and purification of goat lactoferrin from Pichia pastoris expression system. Journal of Food Science. 2007; 72: 67–71. https://doi.org/10.1111/j.1750-3841.2007.00281.x

105. Paramasivam M., Saravanan K., Uma K., Sharma S., Singh T.P., Srinivasan A. Expression, purification and characterization of equine lactoferrin in Pichia pastoris. Protein Expression and Purification. 2002; 26: 28–34. https://doi.org/10.1016/s1046-5928(02)00528-4

106. Wang S.H., Yang T.S., Lin S.M., Tsai M.S., Wu S.C., Mao S. Expression, characterization and purification of recombinant porcine lactoferrin in Pichia pastoris. Protein Expression and Purification. 2002; 25: 41–49. https://doi.org/10.1006/prep.2001.1607

107. Kim H.K. et al. Expression of the cationic antimicrobial peptide lactoferricin fussed with the anionic peptide in Escherichia coli. Applied Microbiology and Biotechnology. 2006; 72: 330–338. https://doi.org/10.1007/s00253-005-0266-5

108. Wang H.K., Zhao X.H., Lu F.P. Heterologous expression of bovine lactoferricin in Pichia mehtanolica. Biochemistry. 2007; 72: 640–643. https://doi.org/10.1134/s0006297907060065

109. Zhang J. et al. Expression of active recombinant human lactoferrin in the milk of transgenic goats. Protein Expression and Purification. 2008; 57: 127–135. https://doi.org/10.1016/j.pep.2007.10.015

110. Han Z.S. et al. High-level expression of human lactoferrin in the milk of goats by using replication-defective adenoviral vectors. Protein Expression and Purification. 2007; 53: 225–231. https://doi.org/10.1016/j.pep.2006.11.019

111. Van Berkel P. et al. Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nature Biotechnology. 2002; 20: 484–487. https://doi.org/10.1038/nbt0502-484

112. Hyvӧnen P. et al. Transgenic cows that produce recombinant human lactoferrin in milk are not protected from experimental Escherichia coli intramammary infection. Infection and Immunity. 2006; 74: 6206–6212. https://doi.org/10.1128/IAI.00238-06

113. Nuijens J.H. et al. Characterization of recombinant human lactoferrin secrete in milk of transgenic mice. Journal of Biological Chemistry. 1997; 272: 8802–8807. https://doi.org/10.1074/jbc.272.13.8802

114. Han Z.S. et al. Adenoviral vector mediates high expression levels of human lactoferrin in the milk of rabbits. Journal of Microbiology and Biotechnology. 2008; 18: 153–159.

115. Budevich A. Prospects for recombinant human lactoferrin obtained from the milk of goat producers. Science and Innovation. 2016; (6): 29–32 (in Russian). https://www.elibrary.ru/wdmzll

116. Tomita M., Wakabayashi H., Shin K., Yamauchi K., Yaeshima T., Iwatsuki K. Twenty-five years of research on bovine lactoferrin applications. Biochimie. 2008; 91(1): 52–57. https://doi.org/10.1016/j.biochi.2008.05.021

117. Coşkun N., Sarıtaş S., Jaouhari Y., Bordiga M., Karav S. The Impact of Freeze Drying on Bioactivity and Physical Properties of Food Products. Applied Sciences. 2024; 14: 9183.

118. Vishwanath-Deutsch R. et al. A review of the safety evidence on recombinant human lactoferrin for use as a food ingredient. Food and Chemical Toxicology. 2024; 189: 114727. https://doi.org/10.1016/j.fct.2024.114727

119. Magnuson B. et al. Review of the regulation and safety assessment of food substances in various countries and jurisdictions. Food Additives & Contaminants: Part A: Chemistry, Analysis, Control, Exposure & Risk Assessment. 2013; 30(7): 1147–220. https://doi.org/10.1080/19440049.2013.795293

120. Richardson V., Freeman E., Fitzpatrick L., Amirat L., Kubo M., Li M. Essential Guide to Food Additives. Chapter 5. Legislation for Food Additives Outside Europe. 2013; 65–90. https://doi.org/10.1039/9781849734981-00065

121. Kwon Y., López-Garcia R., Socolovsky S., Magnuson B. Global regulations for the use of food additives and processing aids. In book: Present Knowledge in Food Safety, 2023; 170–193. https://doi.org/10.1016/B978-0-12-819470-6.00067-6

122. Wakabayashi H., Yamauchi K., Abe F. Quality Control of Commercial Bovine Lactoferrin. Biometals. 2018; 31: 313–319.

123. Rebezov Ya.M., Rebezov M.B., Medvedeva U.Yu. Prospects for the use of lactoferrin in animal husbandry. Agrarian science. 2026; (2):40-59. (In Russian) https://doi.org/10.32634/0869-8155-2026-403-02-40-59